PARISNeoadjvant chemotherapy with the combination of
paclitaxel (Taxol) and doxorubicin gave a pathologic complete
response rate of 16% in a phase II randomized multicenter French
clinical trial of women with previously untreated breast cancers.
Patients treated with the taxane combination had higher pathologic
and clinical response rates than patients given the combination of
doxorubicin (Adriamycin) and cyclophosphamide (AC).
Additionally, more patients treated with paclitaxel and doxorubicin
qualified for breast-conserving surgery, compared with patients in
the doxorubicin-cyclophosphamide arm.
The combination of paclitaxel and doxorubicin is clinically
active in the neoadjuvant setting, Veronique Dieras, MD, a
breast cancer specialist in the medical oncology service at the Curie
Institute, said at a general session of the 21st Annual San Antonio
Breast Cancer Symposium.
She noted that a number of issues still must be resolved. We
need to improve the pathologic response rate, since that is a more
reliable indicator of outcome. We also need to identify critical
factors associated with response so that we can optimize therapy.
However, the results we obtained with this combination are encouraging.
Dr. Dieras reported data from a trial that had as its primary
objective pathologic complete response rate for each neoadjuvant
combination therapy, as determined prior to definitive surgery and
Secondary objectives included the objective clinical response rate,
disease-free survival, and overall survival. Dr. Dieras reported data
on pathologic and clinical response rates.
The trial included patients who had stage T2-3, N0-1, M0 previously
untreated breast cancer. Patients were stratified according to center
and tumor size (T2 or T3).
Investigators randomized the patients to one of two neoadjuvant
regimens: doxorubicin 60 mg/m² as an IV bolus followed by
paclitaxel 200 mg/m² as a 3-hour infusion, or the same dose of
doxorubicin plus cyclophosphamide 600 mg/m² IV bolus.
Patients were randomized in a 2:1 ratio to the paclitaxel-containing
combination vs the combination containing cyclophosphamide. Treatment
was repeated every 3 weeks for a total of four cycles, followed by
surgery, then radiotherapy.
The trial design incorporated an interim analysis that allowed for
termination if specific endpoint criteria were met: fewer than three
complete pathologic responses in the first 40 patients enrolled in
the cyclophosphamide arm or fewer than seven complete responses in
the first 80 patients enrolled in the paclitaxel arm. Without
premature termination, investigators planned to enroll a total of 240
patients (160 receiving doxorubicin-paclitaxel and 80 receiving AC).
The trial was terminated after the interim analysis showed only two
pathologic complete responses in the cyclophosphamide cohort. In
contrast, 11 of the initial 80 paclitaxel-treated patients had a
Dr. Dieras reported findings in a total of 200 patients, 67
randomized to the doxorubicin-cyclophospha-mide regimen and 133
treated with doxorubicin-paclitaxel.
Pathologic complete responses occurred in 16% of the
doxorubicin-paclitaxel group, compared with 10% of the doxorubicin-cyclophosphamide
cohort. The definition of complete response encompassed no evidence
of residual disease (6% with paclitaxel and 4% with
cyclophosphamide), noninvasive residual cancer, or ductal carcinoma
in situ (DCIS).
Objective clinical responses occurred in 85% of the
doxorubicin-paclitaxel group, including complete responses in 18%. In
the doxorubicin-cyclophosphamide cohort, the overall response rate
was 66%, including complete responses in 6% of patients.
Treatment with doxorubicin-paclitaxel led to conservative breast
surgery in 58% of cases, compared with 45% of patients in the
These results are encouraging and will provide the basis for
further investigation of the combination of paclitaxel and
doxorubicin in the neoadjuvant setting, Dr. Dieras said.